The retinal pigment epithelial (RPE) cell plays a basic role in maintaining the structural and physiological integrity of the neural retina. We have isolated and propagated RPE cells in vitro and have developed monoclonal antibodies directed against human RPE cells. We are using these techniques and reagents to evaluate molecular, biochemical, and biological properties of the RPE cells. Because the monoclonal antibodies detect epitopes present solely on RPE cells, they provide us with the unique opportunity to evaluate a variety of aspects of RPE cell development and function. Studies on RPE cell development indicate that the epitopes appear only after the cells have begun terminal differentiation. Moreover, studies on RPE migration also demonstrate the value of these antibodies in evaluating epiretinal membrane formation. The RPE epitope is a 67 kD protein that is closely associated with the microsomal membrane. We have isolated a cDNA clone that codes for a protein which matches no other sequence in the data bases. Studies are also in progress to propagate and transplant RPE cells in various animals. We have propagated human RPE cells in vitro and evaluated their ability to respond to cytokine activation. RPE cells respond to retinal aberrations by dying, proliferating, migrating, losing phagocytic function, expressing major histocompatibility complex (MHC) class II antigens, and presenting antigens to T lymphocytes. The techniques and reagents obtained in these studies allow us to evaluate the mechanisms involved in aberrant RPE cell responses. Moreover, they provide the framework to evaluate RPE cell transplantation.